CodeID	Tissue/Cell type	Variant	Samples	Type of array	GEO Ref	Comments	PIs
DIJ	Substantia Nigra	not specified	15 disease, 8 control	Affymetrix Human Genome U133 Plus 2.0 Array	GSE49036	Has some Braak staging	Dijkstra AA, Ingrassia AI, de Menezes RX, van Kesteren RE, Rozemuller AM, Heutink P, vandeBerg WJ
FFR	Substantia Nigra	not specified	9 replicates for the controls and 16 replicates for the Parkinson’s disease patients	Affymetrix Human Genome U133 Plus 2.0 Array	GSE7621		Ffrench-Mullen JM
MOR.SN	Substantia nigra, split into medial and lateral portions	sporadic	15 samples of medial parkinsonian SN, 9 samples of lateral parkinsonian SN (24), 8 medial nigra control samples and 7 lateral nigra control samples(15)	Affymetrix Human Genome U133A Array	GSE8397	Age and sex	Moran LB, Graeber MB
MID1	Substantia Nigra pars compacta	not specified	10 PD brain samples and 8 control	Affymetrix Human Genome U133 Plus 2.0 Array	GSE20141		Middleton FA, Kim PD, Zhang-James Y, Davis RL
MID2	Whole substantia nigra	not specified	18 controls, 11 patients	Affymetrix Human Genome U133A Array	GSE20292	Age and sex	Middleton FA, James M, Zhang Y, Davis RL
DUM	Cortex (BA9)	not specified	29 PD, 44 neurologically normal controls	Illumina HiSeq 2000	GSE68719	Have age of death, sex, and some samples have corresponding proteomics	Dumitriu A, Golji J, Labadorf AT, Gao B, Beach TG, Myers RH, Longo KA, Latourelle JC
MOR.FC	Frontal cortex	sporadic	3 Controls 5 Patients	Affymetrix Human Genome U133A Array	GSE8397	Age and sex	Moran LB, Graeber MB
LEW	Dorsal Nucleus of the Vagus Nerve	not specified	6 PD samples and 4 controls	Affymetrix Human Genome U133A 2.0 Array	GSE19587	Age and sex	lewandowski nm, small sa
MID3	Prefrontal cortex	not specified	15 controls 14 patients	Affymetrix Human Genome U133A Array	GSE20168	Age and sex	Middleton FA, James M, Zhang Y, Davis RL
MID4	Putamen	not specified	20 controls and 15 patients	Affymetrix Human Genome U133A Array	GSE20291	Age and sex	Middleton FA, James M, Zhang Y, Davis RL
BOT1	Locus Coeruleus	LRRK2	4 controls and 2 patients	Affymetrix Human Exon 1.0 ST Array	GSE34516	LC does degenerate in PD. Main source of noradrenaline.	Botta-Orfila T, Sánchez-Pla A, Fernández M, Carmona F, Ezquerra M, Tolosa E
BOT2	Putamen	LRRK2	5 controls and 3 patients	Affymetrix Human Exon 1.0 ST Array	GSE23290	NA	Botta-Orfila T, Tolosa E, Gelpi E, Sànchez-Pla A, Martí M, Valldeoriola F, Fernández M, Carmona F, Ezquerra M

Quality Control - PD_QC.R

Checked data distribution using PCA and boxplots. Some of the datasets have quite mixed samples wereas others separate quite nicely into controls and patients. Boxplots didn’t suggest any samples were outliers.

Common DEGs

As before, I ran either Limma or DESeq2 and looked for common fold change direction across all 10 datasets. Filtering populations I used were ALS samples (for neurodegeneration), familial blood (for any general familial PD signal + tissue non-specific), and sporadic blood (for generic sporadic signal + tissue non-specific).

Overlap minus these filtration datasets left 210 genes this time (ALS_sfblood_ALLgenes.txt). Overlapping with Malacards PD genes shows presence of 6 PD-associated genes, including alpha synuclein itself.

> intersect(resultsup, PDgenes)
[1] "MSX1" "SPR" 
> intersect(resultsdown, PDgenes)
[1] "SNCA"    "ALDH1A1" "UCHL1"   "CYCS"

Functional Enrichment

Functional enrichment in EnrichR for upregulated and downregulated genes.

Upregulated signal isn’t entirely clear; a number of signalling and DNA-binding pathways are enriched but not with the strongest p values. Alternatively there is quite a strong signal in the downregulated genes. A number of neurodegenerative pathways (inc Parkinson’s disease) are enriched, as well as the electron transport chain/mitochondrial processes (mitochondrion (GO:0005739) padj = 4.711e-8, 23 genes). GO Biological Process also implicates autophagy, which highlights the presence of CHMP2B - a causative ALS/FTLD gene.

VarElect of cDEGs

Symbol	Description	Category	GIFTs	Matched Phenotypes	Matched Phenotypes Scount	Global Rank (Total Genes 11967)	Score
SNCA	Synuclein Alpha	Protein Coding	61	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	2	378.27
UCHL1	Ubiquitin C-Terminal Hydrolase L1	Protein Coding	62	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	7	209.64
CYCS	Cytochrome C, Somatic	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	63	63.23
NDUFV2	NADH:Ubiquinone Oxidoreductase Core Subunit V2	Protein Coding	53	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	106	51.16
ALDH1A1	Aldehyde Dehydrogenase 1 Family Member A1	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	153	42.23
SPR	Sepiapterin Reductase	Protein Coding	58	Parkinson’s Disease, LRRK2, late-onset	3	126	40.38
MSX1	Msh Homeobox 1	Protein Coding	55	Parkinson’s Disease, LRRK2, late-onset	3	169	33.61
NDUFS1	NADH:Ubiquinone Oxidoreductase Core Subunit S1	Protein Coding	56	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	213	28.87
NDUFS3	NADH:Ubiquinone Oxidoreductase Core Subunit S3	Protein Coding	56	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	236	26.54
SYT11	Synaptotagmin 11	Protein Coding	50	Parkinson’s Disease, LRRK2, neurodegeneration	3	239	22.93
CASP7	Caspase 7	Protein Coding	59	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	309	21.45
TOMM20	Translocase Of Outer Mitochondrial Membrane 20	Protein Coding	48	Parkinson’s Disease, LRRK2, neurodegeneration	3	362	16.56
MFN2	Mitofusin 2	Protein Coding	59	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	424	16.55
IGF1R	Insulin Like Growth Factor 1 Receptor	Protein Coding	66	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	435	16.27
MAP1B	Microtubule Associated Protein 1B	Protein Coding	51	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	474	15.18
TMEM126B	Transmembrane Protein 126B	Protein Coding	47	Parkinson’s Disease, LRRK2	2	363	13.45
PTS	6-Pyruvoyltetrahydropterin Synthase	Protein Coding	57	Parkinson’s Disease, late-onset, neurodegeneration	3	556	11.88
CASP6	Caspase 6	Protein Coding	57	Parkinson’s Disease, LRRK2, neurodegeneration	3	573	11.74
RAB7A	RAB7A, Member RAS Oncogene Family	Protein Coding	58	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	759	11.00
PPP2R2B	Protein Phosphatase 2 Regulatory Subunit Bbeta	Protein Coding	55	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	788	10.69
PYROXD1	Pyridine Nucleotide-Disulphide Oxidoreductase Domain 1	Protein Coding	44	Parkinson’s Disease, late-onset	2	487	10.60
AGRP	Agouti Related Neuropeptide	Protein Coding	51	late-onset, neurodegeneration	2	504	10.27
AIFM1	Apoptosis Inducing Factor Mitochondria Associated 1	Protein Coding	59	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	898	9.70
FLT1	Fms Related Tyrosine Kinase 1	Protein Coding	62	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	952	9.26
RTN4	Reticulon 4	Protein Coding	54	LRRK2, late-onset, neurodegeneration	3	792	9.21
DYNC1H1	Dynein Cytoplasmic 1 Heavy Chain 1	Protein Coding	54	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	965	9.11
TUBA4A	Tubulin Alpha 4a	Protein Coding	56	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	968	9.09
CHMP2B	Charged Multivesicular Body Protein 2B	Protein Coding	53	Parkinson’s Disease, late-onset, neurodegeneration	3	894	8.43
RGS2	Regulator Of G Protein Signaling 2	Protein Coding	51	Parkinson’s Disease, LRRK2, neurodegeneration	3	944	8.07
HIST1H1C	Histone Cluster 1 H1 Family Member C	Protein Coding	48	Parkinson’s Disease	1	520	7.11
PAWR	Pro-Apoptotic WT1 Regulator	Protein Coding	48	Parkinson’s Disease, neurodegeneration	2	982	6.36
MS4A6A	Membrane Spanning 4-Domains A6A	Protein Coding	45	Parkinson’s Disease, late-onset, neurodegeneration	3	1259	6.26
MYO1C	Myosin IC	Protein Coding	53	Parkinson’s Disease, LRRK2, neurodegeneration	3	1362	5.78
SUMO1	Small Ubiquitin-Like Modifier 1	Protein Coding	56	Parkinson’s Disease, neurodegeneration	2	1277	5.04
ACLY	ATP Citrate Lyase	Protein Coding	53	Parkinson’s Disease, LRRK2, neurodegeneration	3	1577	4.91
SDHA	Succinate Dehydrogenase Complex Flavoprotein Subunit A	Protein Coding	56	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	1850	4.77
PGF	Placental Growth Factor	Protein Coding	54	LRRK2, late-onset	2	1361	4.72
TRADD	TNFRSF1A Associated Via Death Domain	Protein Coding	51	Parkinson’s Disease, LRRK2, neurodegeneration	3	1694	4.57
HSPA1L	Heat Shock Protein Family A (Hsp70) Member 1 Like	Protein Coding	52	Parkinson’s Disease, LRRK2	2	1457	4.38
GABBR2	Gamma-Aminobutyric Acid Type B Receptor Subunit 2	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset	3	1880	4.04
PGAM1	Phosphoglycerate Mutase 1	Protein Coding	54	Parkinson’s Disease, neurodegeneration	2	1602	3.95
ATP6V1E1	ATPase H+ Transporting V1 Subunit E1	Protein Coding	52	Parkinson’s Disease, LRRK2, late-onset	3	2008	3.70
FZD5	Frizzled Class Receptor 5	Protein Coding	57	Parkinson’s Disease, LRRK2	2	1718	3.67
MRPS22	Mitochondrial Ribosomal Protein S22	Protein Coding	50	Parkinson’s Disease, neurodegeneration	2	1776	3.54
PLIN2	Perilipin 2	Protein Coding	51	late-onset, neurodegeneration	2	1805	3.47
CIRBP	Cold Inducible RNA Binding Protein	Protein Coding	48	Parkinson’s Disease, LRRK2, neurodegeneration	3	2119	3.38
SNX10	Sorting Nexin 10	Protein Coding	49	Parkinson’s Disease, LRRK2	2	1913	3.22
FABP3	Fatty Acid Binding Protein 3	Protein Coding	54	Parkinson’s Disease, neurodegeneration	2	1947	3.13
BCAT2	Branched Chain Amino Acid Transaminase 2	Protein Coding	53	Parkinson’s Disease, neurodegeneration	2	1987	3.05
ADH1B	Alcohol Dehydrogenase 1B (Class I), Beta Polypeptide	Protein Coding	53	Parkinson’s Disease, late-onset	2	2004	3.03
RARRES2	Retinoic Acid Receptor Responder 2	Protein Coding	50	late-onset	1	1536	2.92
DNAJC24	DnaJ Heat Shock Protein Family (Hsp40) Member C24	Protein Coding	44	LRRK2, late-onset	2	2118	2.76
PRPF4	Pre-MRNA Processing Factor 4	Protein Coding	51	Parkinson’s Disease, LRRK2, neurodegeneration	3	2366	2.55
FLCN	Folliculin	Protein Coding	50	Parkinson’s Disease, late-onset	2	2227	2.46
COPS5	COP9 Signalosome Subunit 5	Protein Coding	51	Parkinson’s Disease, LRRK2, neurodegeneration	3	2450	2.31
ENOPH1	Enolase-Phosphatase 1	Protein Coding	49	Parkinson’s Disease	1	2186	1.83
ZC3HAV1	Zinc Finger CCCH-Type Containing, Antiviral 1	Protein Coding	46	Parkinson’s Disease, neurodegeneration	2	2481	1.81
PLCG1	Phospholipase C Gamma 1	Protein Coding	56	Parkinson’s Disease, LRRK2	2	2492	1.80
STAB1	Stabilin 1	Protein Coding	48	Parkinson’s Disease	1	2218	1.76
HP1BP3	Heterochromatin Protein 1 Binding Protein 3	Protein Coding	44	Parkinson’s Disease, neurodegeneration	2	2528	1.71
MLLT11	MLLT11, Transcription Factor 7 Cofactor	Protein Coding	45	late-onset	1	2261	1.68
AGL	Amylo-Alpha-1, 6-Glucosidase, 4-Alpha-Glucanotransferase	Protein Coding	55	late-onset	1	2261	1.68
MAVS	Mitochondrial Antiviral Signaling Protein	Protein Coding	50	late-onset	1	2261	1.68
TAZ	Tafazzin	Protein Coding	52	late-onset	1	2261	1.68
SLC6A1	Solute Carrier Family 6 Member 1	Protein Coding	57	Parkinson’s Disease, neurodegeneration	2	2545	1.67
STAT4	Signal Transducer And Activator Of Transcription 4	Protein Coding	56	LRRK2, late-onset	2	2559	1.63
EIF4E	Eukaryotic Translation Initiation Factor 4E	Protein Coding	59	Parkinson’s Disease, LRRK2	2	2565	1.62
NIPSNAP1	Nipsnap Homolog 1	Protein Coding	49	Parkinson’s Disease, LRRK2	2	2565	1.62
RAD51C	RAD51 Paralog C	Protein Coding	51	Parkinson’s Disease, LRRK2	2	2573	1.60
NCALD	Neurocalcin Delta	Protein Coding	51	Parkinson’s Disease, LRRK2	2	2573	1.60
LRRC1	Leucine Rich Repeat Containing 1	Protein Coding	44	Parkinson’s Disease, LRRK2	2	2573	1.60
PKNOX1	PBX/Knotted 1 Homeobox 1	Protein Coding	47	Parkinson’s Disease, LRRK2	2	2573	1.60
GABARAPL1	GABA Type A Receptor Associated Protein Like 1	Protein Coding	53	Parkinson’s Disease, neurodegeneration	2	2609	1.51
MAP1LC3B	Microtubule Associated Protein 1 Light Chain 3 Beta	Protein Coding	52	Parkinson’s Disease, neurodegeneration	2	2611	1.50
LYVE1	Lymphatic Vessel Endothelial Hyaluronan Receptor 1	Protein Coding	51	late-onset, neurodegeneration	2	2651	1.41
DYNC1I1	Dynein Cytoplasmic 1 Intermediate Chain 1	Protein Coding	48	Parkinson’s Disease, neurodegeneration	2	2666	1.37
FOXO4	Forkhead Box O4	Protein Coding	51	Parkinson’s Disease, LRRK2	2	2667	1.37
NME3	NME/NM23 Nucleoside Diphosphate Kinase 3	Protein Coding	51	Parkinson’s Disease, neurodegeneration	2	2680	1.33
SERTAD3	SERTA Domain Containing 3	Protein Coding	38	neurodegeneration	1	2476	1.29
USP8	Ubiquitin Specific Peptidase 8	Protein Coding	57	Parkinson’s Disease, LRRK2, neurodegeneration	3	2776	1.27
ATG14	Autophagy Related 14	Protein Coding	43	Parkinson’s Disease	1	2551	1.17
LDLRAD4	Low Density Lipoprotein Receptor Class A Domain Containing 4	Protein Coding	40	Parkinson’s Disease	1	2551	1.17
TAF4	TATA-Box Binding Protein Associated Factor 4	Protein Coding	48	LRRK2, neurodegeneration	2	2778	1.03
RBL1	RB Transcriptional Corepressor Like 1	Protein Coding	51	LRRK2, late-onset	2	2802	0.95
IARS2	Isoleucyl-TRNA Synthetase 2, Mitochondrial	Protein Coding	49	Parkinson’s Disease	1	2681	0.94
KLHL36	Kelch Like Family Member 36	Protein Coding	41	late-onset	1	2683	0.93
ST3GAL5	ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5	Protein Coding	55	late-onset	1	2706	0.88
CLIC2	Chloride Intracellular Channel 2	Protein Coding	49	late-onset	1	2706	0.88
DDX42	DEAD-Box Helicase 42	Protein Coding	46	Parkinson’s Disease	1	2711	0.87
ANXA6	Annexin A6	Protein Coding	53	Parkinson’s Disease	1	2711	0.87
CCDC40	Coiled-Coil Domain Containing 40	Protein Coding	45	Parkinson’s Disease	1	2711	0.87
LAG3	Lymphocyte Activating 3	Protein Coding	44	Parkinson’s Disease	1	2711	0.87
SDCCAG3	Serologically Defined Colon Cancer Antigen 3	Protein Coding	41	Parkinson’s Disease	1	2711	0.87
BCAR3	BCAR3, NSP Family Adaptor Protein	Protein Coding	49	Parkinson’s Disease	1	2711	0.87
IMP4	IMP4, U3 Small Nucleolar Ribonucleoprotein	Protein Coding	42	Parkinson’s Disease	1	2711	0.87
LETMD1	LETM1 Domain Containing 1	Protein Coding	43	Parkinson’s Disease	1	2711	0.87
PTP4A1	Protein Tyrosine Phosphatase Type IVA, Member 1	Protein Coding	51	Parkinson’s Disease	1	2711	0.87
RCC1	Regulator Of Chromosome Condensation 1	Protein Coding	49	LRRK2, neurodegeneration	2	2829	0.86
TXNL1	Thioredoxin Like 1	Protein Coding	47	late-onset	1	2741	0.79
CD84	CD84 Molecule	Protein Coding	51	late-onset	1	2806	0.66
DUSP9	Dual Specificity Phosphatase 9	Protein Coding	50	LRRK2	1	2807	0.66
FHIT	Fragile Histidine Triad	Protein Coding	54	Parkinson’s Disease, late-onset	2	2896	0.61
ANGPT2	Angiopoietin 2	Protein Coding	55	LRRK2, late-onset	2	2901	0.58
INHBB	Inhibin Beta B Subunit	Protein Coding	53	LRRK2, late-onset	2	2901	0.58
CALML4	Calmodulin Like 4	Protein Coding	41	LRRK2	1	2853	0.54
HDAC7	Histone Deacetylase 7	Protein Coding	52	LRRK2	1	2853	0.54
ATP2B2	ATPase Plasma Membrane Ca2+ Transporting 2	Protein Coding	54	LRRK2, neurodegeneration	2	2915	0.52
PPP2R1B	Protein Phosphatase 2 Scaffold Subunit Abeta	Protein Coding	57	LRRK2	1	2905	0.39
RGS4	Regulator Of G Protein Signaling 4	Protein Coding	52	LRRK2	1	2905	0.39
KPNA1	Karyopherin Subunit Alpha 1	Protein Coding	51	Parkinson’s Disease, neurodegeneration	2	2942	0.35
NRXN3	Neurexin 3	Protein Coding	51	neurodegeneration	1	2920	0.34
SARS	Seryl-TRNA Synthetase	Protein Coding	53	neurodegeneration	1	2920	0.34
PGRMC1	Progesterone Receptor Membrane Component 1	Protein Coding	53	neurodegeneration	1	2920	0.34
RDH16	Retinol Dehydrogenase 16 (All-Trans)	Protein Coding	44	LRRK2	1	2936	0.28
SMAD6	SMAD Family Member 6	Protein Coding	54	LRRK2	1	2936	0.28
NFATC4	Nuclear Factor Of Activated T Cells 4	Protein Coding	53	LRRK2	1	2936	0.28
REEP5	Receptor Accessory Protein 5	Protein Coding	46	LRRK2	1	2936	0.28
EFNA4	Ephrin A4	Protein Coding	50	LRRK2	1	2936	0.28
MST1	Macrophage Stimulating 1	Protein Coding	55	LRRK2	1	2936	0.28
FSTL3	Follistatin Like 3	Protein Coding	48	LRRK2	1	2936	0.28
LAMA5	Laminin Subunit Alpha 5	Protein Coding	51	LRRK2	1	2936	0.28
PRC1	Protein Regulator Of Cytokinesis 1	Protein Coding	47	LRRK2	1	2936	0.28
LAMB2	Laminin Subunit Beta 2	Protein Coding	55	LRRK2	1	2936	0.28
ZNF629	Zinc Finger Protein 629	Protein Coding	38	LRRK2	1	2938	0.27
NR6A1	Nuclear Receptor Subfamily 6 Group A Member 1	Protein Coding	50	LRRK2	1	2938	0.27
ATP8A2	ATPase Phospholipid Transporting 8A2	Protein Coding	50	LRRK2	1	2938	0.27
AREL1	Apoptosis Resistant E3 Ubiquitin Protein Ligase 1	Protein Coding	38	LRRK2	1	2938	0.27
ZNF692	Zinc Finger Protein 692	Protein Coding	40	LRRK2	1	2938	0.27
ROBO3	Roundabout Guidance Receptor 3	Protein Coding	52	LRRK2	1	2938	0.27
ACAT2	Acetyl-CoA Acetyltransferase 2	Protein Coding	55	LRRK2	1	2938	0.27
STX2	Syntaxin 2	Protein Coding	48	LRRK2	1	2938	0.27
TCF3	Transcription Factor 3	Protein Coding	55	LRRK2	1	2938	0.27
RAB6B	RAB6B, Member RAS Oncogene Family	Protein Coding	46	LRRK2	1	2938	0.27
DOCK6	Dedicator Of Cytokinesis 6	Protein Coding	50	LRRK2	1	2938	0.27
INSIG2	Insulin Induced Gene 2	Protein Coding	47	LRRK2	1	2938	0.27
DNAJB9	DnaJ Heat Shock Protein Family (Hsp40) Member B9	Protein Coding	45	LRRK2	1	2938	0.27
HLTF	Helicase Like Transcription Factor	Protein Coding	48	LRRK2	1	2938	0.27
VPS4B	Vacuolar Protein Sorting 4 Homolog B	Protein Coding	51	Parkinson’s Disease	1	2952	0.18
SLC23A2	Solute Carrier Family 23 Member 2	Protein Coding	52	Parkinson’s Disease	1	2952	0.18
TULP2	Tubby Like Protein 2	Protein Coding	44	late-onset	1	2955	0.13
ALAS1	5’-Aminolevulinate Synthase 1	Protein Coding	53	late-onset	1	2955	0.13
PTBP2	Polypyrimidine Tract Binding Protein 2	Protein Coding	47	neurodegeneration	1	2959	0.07
ZMYND8	Zinc Finger MYND-Type Containing 8	Protein Coding	46	neurodegeneration	1	2959	0.07
WDYHV1	WDYHV Motif Containing 1	Protein Coding	39	neurodegeneration	1	2959	0.07
FAM193B	Family With Sequence Similarity 193 Member B	Protein Coding	42	neurodegeneration	1	2959	0.07
SEZ6L2	Seizure Related 6 Homolog Like 2	Protein Coding	46	neurodegeneration	1	2959	0.07

Protein Interaction Network

Using the 210 DEGs I seeded a network of 2429 nodes and 4097 edges.

library(biomaRt)

setwd("/Users/clairegreen/Documents/PhD/TDP-43/TDP-43_Code/Results/PPI_Network/")

PPI <- read.table("iref14_Human_UP_noDup_table_nodash.txt", header = T)
braingenes <- read.csv("Zhang_BrainCelltype_Markers_braingenes.csv", header = T)

DEG_list <- readLines("~/Documents/PhD/Parkinsons/Parkinsons_Code/Results/FamilialBlood/ALS_sfblood_ALLgenes.txt")

mart <- useMart("ENSEMBL_MART_ENSEMBL",dataset="hsapiens_gene_ensembl", host="www.ensembl.org")
attributes <- listAttributes(mart)
mart_back <- getBM(attributes =c("hgnc_symbol", "uniprotswissprot"), filters="hgnc_symbol", values=DEG_list,  mart=mart)
genelist_Uniprot <- subset(mart_back, !(mart_back$uniprotswissprot == ""))
setwd("/Users/clairegreen/Documents/PhD/Parkinsons/Parkinsons_Code/Results/FamilialBlood/")
write.csv(genelist_Uniprot, "martback.csv", row.names = F)

# IDENTIFY MISSING GENES AND FIND UNIPROT CODES FOR THEM. NB SOME GENES MAY NOT BE PROTEIN CODING #

mart_table <- read.csv("martback.csv", header = T) #A table with the uniprot codes for the DEGs
uniprot_gene <- mart_table$uniprotswissprot

DEG_PPI <- subset(PPI, PPI$V1 %in% uniprot_gene | PPI$V2 %in% uniprot_gene)
rownames(DEG_PPI) <- 1:nrow(DEG_PPI)

write.csv(DEG_PPI, "DEG_PPI_famBlood.csv", row.names = F)

## Convert Uniprot ID to HGNC symbol. Biomart jumbles output so
## Go To https://biodbnet-abcc.ncifcrf.gov/db/db2db.php submit each column of names. Select Uniprot Accession for input and Gene Symbol for output.
# Select "NO" for remove duplicate input valies

DEG_PPI <- read.csv("DEG_PPI_famBlood.csv")

DEG_PPI <- subset(DEG_PPI, DEG_PPI$Gene1 !="-")
DEG_PPI <- subset(DEG_PPI, DEG_PPI$Gene2 !="-")

write.csv(DEG_PPI, "FinalPDPPI.csv", row.names = F, quote = F)

PPI Network

Common Coexpression

I ran common coexpression again using Sharc. DUM was again removed because it had ~100,000 fewer edges than the other datasets. I then plotted the distributions of rho values to check they were normally distributed:

From this it is clear that the LEW and MOR.FC datasets do not have the power for a normal coexpression distribution. These two datasets were therefore removed from the common coexpression edge analysis.

When looking for a common edge, I tried three different minimum Rho values; 0.5, 0.4, and 0.3.

Threshold of 0.5

Threshold of 0.4

Threshold of 0.3

The largest connected component consists of 82 genes and 95 edges.

Largest Connected Component of 0.3

IrefIndex 14.0 PPI between PD Malacards and LCC

Here we can see that there are 25 LCC proteins which forming 45 PPI relationships with 25 PD Malacard genes (1 overlap of PARK7)

VarElect

Although already noted, the VarElect results clearly show the membership of PARK7 in the network. The interesting thing about PARK7 being here is that it is more commonly associated with early-onset or juvenile Parkinson’s disease. Another interesting point is that, although PARK7 PD is early-onset, it’s classified by UniProt as having “slow progression and initial good response to levodopa”.

CYCS or Cytochrome C, Somatic, is a small heme protein that functions as a central component of the electron transport chain in mitochondria. It is closely related to Parkinson’s disease in the literature due to its apparent malfuction in the disease.

Direct VarElect Results

Symbol	Description	Category	GIFTs	Matched Phenotypes	Matched Phenotypes Scount	Global Rank (Total Genes 11967)	Score
PARK7	Parkinsonism Associated Deglycase	Protein Coding	56	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	5	270.87
CYCS	Cytochrome C, Somatic	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	63	63.23
UBE2E3	Ubiquitin Conjugating Enzyme E2 E3	Protein Coding	51	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	119	48.51
STXBP1	Syntaxin Binding Protein 1	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	370	18.76
VDR	Vitamin D Receptor	Protein Coding	61	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	380	18.20
COX5A	Cytochrome C Oxidase Subunit 5A	Protein Coding	53	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	536	13.99
PGK1	Phosphoglycerate Kinase 1	Protein Coding	59	Parkinson’s Disease, late-onset, neurodegeneration	3	513	12.40
NDUFA8	NADH:Ubiquinone Oxidoreductase Subunit A8	Protein Coding	50	Parkinson’s Disease, LRRK2, late-onset	3	641	10.77
EIF4EBP1	Eukaryotic Translation Initiation Factor 4E Binding Protein 1	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset	3	715	9.90
DLD	Dihydrolipoamide Dehydrogenase	Protein Coding	61	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	899	9.68
PSMC6	Proteasome 26S Subunit, ATPase 6	Protein Coding	50	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	925	9.51
PLA2G2A	Phospholipase A2 Group IIA	Protein Coding	56	Parkinson’s Disease, late-onset, neurodegeneration	3	770	9.43
RTN4	Reticulon 4	Protein Coding	54	LRRK2, late-onset, neurodegeneration	3	792	9.21
NDUFA5	NADH:Ubiquinone Oxidoreductase Subunit A5	Protein Coding	51	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	998	8.87
UQCRC2	Ubiquinol-Cytochrome C Reductase Core Protein 2	Protein Coding	55	Parkinson’s Disease, LRRK2, neurodegeneration	3	1033	7.46
RAB11A	RAB11A, Member RAS Oncogene Family	Protein Coding	55	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	1321	6.93
SFXN1	Sideroflexin 1	Protein Coding	47	Parkinson’s Disease, LRRK2, neurodegeneration	3	1241	6.34
RAB1A	RAB1A, Member RAS Oncogene Family	Protein Coding	51	Parkinson’s Disease, LRRK2, neurodegeneration	3	1282	6.14
PSMC5	Proteasome 26S Subunit, ATPase 5	Protein Coding	51	Parkinson’s Disease, LRRK2, neurodegeneration	3	1311	6.03
PSMA7	Proteasome Subunit Alpha 7	Protein Coding	55	Parkinson’s Disease, LRRK2, neurodegeneration	3	1482	5.27
SUMO1	Small Ubiquitin-Like Modifier 1	Protein Coding	56	Parkinson’s Disease, neurodegeneration	2	1277	5.04
ACLY	ATP Citrate Lyase	Protein Coding	53	Parkinson’s Disease, LRRK2, neurodegeneration	3	1577	4.91
SDHA	Succinate Dehydrogenase Complex Flavoprotein Subunit A	Protein Coding	56	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	1850	4.77
PSMD6	Proteasome 26S Subunit, Non-ATPase 6	Protein Coding	47	Parkinson’s Disease, LRRK2, neurodegeneration	3	1696	4.56
UQCRC1	Ubiquinol-Cytochrome C Reductase Core Protein 1	Protein Coding	50	Parkinson’s Disease, LRRK2, neurodegeneration	3	1746	4.43
PDHB	Pyruvate Dehydrogenase E1 Beta Subunit	Protein Coding	56	Parkinson’s Disease, LRRK2, neurodegeneration	3	1781	4.32
NR4A1	Nuclear Receptor Subfamily 4 Group A Member 1	Protein Coding	55	Parkinson’s Disease, LRRK2, neurodegeneration	3	1865	4.09
IARS	Isoleucyl-TRNA Synthetase	Protein Coding	55	Parkinson’s Disease, neurodegeneration	2	1597	3.97
ATP6V1E1	ATPase H+ Transporting V1 Subunit E1	Protein Coding	52	Parkinson’s Disease, LRRK2, late-onset	3	2008	3.70
MAP2K1	Mitogen-Activated Protein Kinase Kinase 1	Protein Coding	65	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	2197	3.60
PPP2CA	Protein Phosphatase 2 Catalytic Subunit Alpha	Protein Coding	56	Parkinson’s Disease, LRRK2, neurodegeneration	3	2050	3.58
TRIM37	Tripartite Motif Containing 37	Protein Coding	51	neurodegeneration	1	1309	3.49
UQCRFS1	Ubiquinol-Cytochrome C Reductase, Rieske Iron-Sulfur Polypeptide 1	Protein Coding	51	Parkinson’s Disease, LRRK2, neurodegeneration	3	2137	3.31
VAV1	Vav Guanine Nucleotide Exchange Factor 1	Protein Coding	57	LRRK2, late-onset	2	1938	3.15
RUNX2	Runt Related Transcription Factor 2	Protein Coding	57	late-onset	1	1481	3.04
CUL3	Cullin 3	Protein Coding	55	Parkinson’s Disease, LRRK2, neurodegeneration	3	2349	2.62
PPIA	Peptidylprolyl Isomerase A	Protein Coding	57	Parkinson’s Disease, LRRK2, neurodegeneration	3	2366	2.55
UBE2K	Ubiquitin Conjugating Enzyme E2 K	Protein Coding	51	Parkinson’s Disease, LRRK2, neurodegeneration	3	2388	2.49
COPS5	COP9 Signalosome Subunit 5	Protein Coding	51	Parkinson’s Disease, LRRK2, neurodegeneration	3	2450	2.31
PDHA1	Pyruvate Dehydrogenase E1 Alpha 1 Subunit	Protein Coding	59	Parkinson’s Disease, LRRK2, neurodegeneration	3	2547	2.04
DDX1	DEAD-Box Helicase 1	Protein Coding	51	Parkinson’s Disease, neurodegeneration	2	2528	1.71
ANXA7	Annexin A7	Protein Coding	51	late-onset, neurodegeneration	2	2571	1.60
YARS	Tyrosyl-TRNA Synthetase	Protein Coding	53	late-onset, neurodegeneration	2	2576	1.60
PSMD12	Proteasome 26S Subunit, Non-ATPase 12	Protein Coding	49	Parkinson’s Disease, LRRK2, neurodegeneration	3	2710	1.50
EPS15	Epidermal Growth Factor Receptor Pathway Substrate 15	Protein Coding	54	Parkinson’s Disease, LRRK2	2	2701	1.26
PIK3CB	Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta	Protein Coding	57	LRRK2, neurodegeneration	2	2746	1.11
MDH1	Malate Dehydrogenase 1	Protein Coding	55	Parkinson’s Disease, neurodegeneration	2	2770	1.04
ATP6V1B2	ATPase H+ Transporting V1 Subunit B2	Protein Coding	56	LRRK2, neurodegeneration	2	2775	1.03
GABARAPL2	GABA Type A Receptor Associated Protein Like 2	Protein Coding	55	Parkinson’s Disease	1	2652	0.99
IARS2	Isoleucyl-TRNA Synthetase 2, Mitochondrial	Protein Coding	49	Parkinson’s Disease	1	2681	0.94
STRAP	Serine/Threonine Kinase Receptor Associated Protein	Protein Coding	45	LRRK2, neurodegeneration	2	2823	0.88
FOSL1	FOS Like 1, AP-1 Transcription Factor Subunit	Protein Coding	52	LRRK2, neurodegeneration	2	2826	0.87
ICK	Intestinal Cell Kinase	Protein Coding	53	Parkinson’s Disease	1	2711	0.87
TXNL1	Thioredoxin Like 1	Protein Coding	47	late-onset	1	2741	0.79
TMEM30A	Transmembrane Protein 30A	Protein Coding	46	Parkinson’s Disease, LRRK2	2	2895	0.62
RRAS	RAS Related	Protein Coding	52	LRRK2	1	2853	0.54
PRDM4	PR/SET Domain 4	Protein Coding	43	LRRK2	1	2853	0.54
NPTN	Neuroplastin	Protein Coding	49	neurodegeneration	1	2878	0.49
ATP6V1H	ATPase H+ Transporting V1 Subunit H	Protein Coding	48	LRRK2	1	2905	0.39
NME1	NME/NM23 Nucleoside Diphosphate Kinase 1	Protein Coding	57	neurodegeneration	1	2920	0.34
REEP5	Receptor Accessory Protein 5	Protein Coding	46	LRRK2	1	2936	0.28
SUCLA2	Succinate-CoA Ligase ADP-Forming Beta Subunit	Protein Coding	57	LRRK2	1	2936	0.28
BCAS2	BCAS2, Pre-MRNA Processing Factor	Protein Coding	46	LRRK2	1	2938	0.27
SF3A2	Splicing Factor 3a Subunit 2	Protein Coding	46	LRRK2	1	2938	0.27
HLTF	Helicase Like Transcription Factor	Protein Coding	48	LRRK2	1	2938	0.27
RAB22A	RAB22A, Member RAS Oncogene Family	Protein Coding	44	LRRK2	1	2938	0.27
RAN	RAN, Member RAS Oncogene Family	Protein Coding	54	neurodegeneration	1	2958	0.10
PTBP2	Polypyrimidine Tract Binding Protein 2	Protein Coding	47	neurodegeneration	1	2959	0.07

Indirect VarElect Results

Implicated Symbol	Implicating Symbol	Description	Category	GIFTs	Matched Phenotypes	Matched Phenotypes Count	Global Rank (Total Genes 11967)	Score (Implicated)
UBE2V2	PRKN	Parkin RBR E3 Ubiquitin Protein Ligase	Protein Coding	47	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	3	23.14
UBE2V2	RPS27A	Ribosomal Protein S27a	Protein Coding	53	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	45	23.14
UBE2V2	FBXO7	F-Box Protein 7	Protein Coding	50	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	16	23.14
UBE2V2	UCHL1	Ubiquitin C-Terminal Hydrolase L1	Protein Coding	62	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	7	23.14
UBE2V2	UBE2E2	Ubiquitin Conjugating Enzyme E2 E2	Protein Coding	49	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	145	23.14
SNAP91	SNCA	Synuclein Alpha	Protein Coding	61	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	2	13.14
SNAP91	PRKN	Parkin RBR E3 Ubiquitin Protein Ligase	Protein Coding	47	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	3	13.14
SNAP91	SYNJ1	Synaptojanin 1	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	33	13.14
SNAP91	DNAJC6	DnaJ Heat Shock Protein Family (Hsp40) Member C6	Protein Coding	51	Parkinson’s Disease, LRRK2, late-onset	3	27	13.14
SNAP91	UCHL1	Ubiquitin C-Terminal Hydrolase L1	Protein Coding	62	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	7	13.14
TERF2IP	UCHL1	Ubiquitin C-Terminal Hydrolase L1	Protein Coding	62	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	7	12.55
TERF2IP	SNCA	Synuclein Alpha	Protein Coding	61	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	2	12.55
TERF2IP	AKT1	AKT Serine/Threonine Kinase 1	Protein Coding	65	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	79	12.55
TERF2IP	RPS27A	Ribosomal Protein S27a	Protein Coding	53	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	45	12.55
TERF2IP	TBP	TATA-Box Binding Protein	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	40	12.55
PYCARD	BAX	BCL2 Associated X, Apoptosis Regulator	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	107	9.78
PYCARD	NLRP3	NLR Family Pyrin Domain Containing 3	Protein Coding	56	Parkinson’s Disease, late-onset	2	222	9.78
PYCARD	PRKN	Parkin RBR E3 Ubiquitin Protein Ligase	Protein Coding	47	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	3	9.78
PYCARD	CASP3	Caspase 3	Protein Coding	61	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	56	9.78
PYCARD	SQSTM1	Sequestosome 1	Protein Coding	59	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	48	9.78
SRPRB	SNCA	Synuclein Alpha	Protein Coding	61	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	2	8.42
SRPRB	PRKN	Parkin RBR E3 Ubiquitin Protein Ligase	Protein Coding	47	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	3	8.42
SRPRB	RPS27A	Ribosomal Protein S27a	Protein Coding	53	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	45	8.42
SRPRB	UCHL1	Ubiquitin C-Terminal Hydrolase L1	Protein Coding	62	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	7	8.42
SRPRB	SNCAIP	Synuclein Alpha Interacting Protein	Protein Coding	52	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	8	8.42
EIF1B	EIF4G1	Eukaryotic Translation Initiation Factor 4 Gamma 1	Protein Coding	55	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	36	7.94
EIF1B	UCHL1	Ubiquitin C-Terminal Hydrolase L1	Protein Coding	62	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	7	7.94
EIF1B	RPS27A	Ribosomal Protein S27a	Protein Coding	53	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	45	7.94
EIF1B	SOD2	Superoxide Dismutase 2	Protein Coding	60	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	78	7.94
EIF1B	GAPDH	Glyceraldehyde-3-Phosphate Dehydrogenase	Protein Coding	58	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	98	7.94
MRPL15	PARK7	Parkinsonism Associated Deglycase	Protein Coding	56	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	5	7.78
MRPL15	RPS27A	Ribosomal Protein S27a	Protein Coding	53	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	45	7.78
MRPL15	NDUFS4	NADH:Ubiquinone Oxidoreductase Subunit S4	Protein Coding	52	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	31	7.78
MRPL15	TH	Tyrosine Hydroxylase	Protein Coding	62	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	24	7.78
MRPL15	EIF4G1	Eukaryotic Translation Initiation Factor 4 Gamma 1	Protein Coding	55	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	36	7.78
LYL1	GDNF	Glial Cell Derived Neurotrophic Factor	Protein Coding	59	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	52	7.74
LYL1	PLAU	Plasminogen Activator, Urokinase	Protein Coding	63	LRRK2, late-onset	2	162	7.74
LYL1	NFKB1	Nuclear Factor Kappa B Subunit 1	Protein Coding	63	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	409	7.74
LYL1	ZEB1	Zinc Finger E-Box Binding Homeobox 1	Protein Coding	57	late-onset	1	273	7.74
LYL1	BAX	BCL2 Associated X, Apoptosis Regulator	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	107	7.74
XRCC2	RPS27A	Ribosomal Protein S27a	Protein Coding	53	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	45	6.43
XRCC2	NBN	Nibrin	Protein Coding	55	Parkinson’s Disease, late-onset, neurodegeneration	3	388	6.43
XRCC2	TP53	Tumor Protein P53	Protein Coding	65	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	201	6.43
XRCC2	COMT	Catechol-O-Methyltransferase	Protein Coding	61	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	34	6.43
XRCC2	ATM	ATM Serine/Threonine Kinase	Protein Coding	64	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	498	6.43
BMP8B	PLA2G6	Phospholipase A2 Group VI	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	12	6.27
BMP8B	BDNF	Brain Derived Neurotrophic Factor	Protein Coding	59	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	42	6.27
BMP8B	MAPK14	Mitogen-Activated Protein Kinase 14	Protein Coding	62	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	89	6.27
BMP8B	IL10	Interleukin 10	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	243	6.27
BMP8B	GDNF	Glial Cell Derived Neurotrophic Factor	Protein Coding	59	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	52	6.27
LAPTM4B	GBA	Glucosylceramidase Beta	Protein Coding	59	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	11	5.59
LAPTM4B	ABCB1	ATP Binding Cassette Subfamily B Member 1	Protein Coding	61	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	449	5.59
LAPTM4B	NEDD4	Neural Precursor Cell Expressed, Developmentally Down-Regulated 4, E3 Ubiquitin Protein Ligase	Protein Coding	55	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	669	5.59
LAPTM4B	SLC11A2	Solute Carrier Family 11 Member 2	Protein Coding	58	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	132	5.59
LAPTM4B	NFE2L2	Nuclear Factor, Erythroid 2 Like 2	Protein Coding	56	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	351	5.59
ADSS	GBA	Glucosylceramidase Beta	Protein Coding	59	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	11	4.39
ADSS	PLA2G6	Phospholipase A2 Group VI	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	12	4.39
ADSS	GAD1	Glutamate Decarboxylase 1	Protein Coding	61	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	120	4.39
ADSS	APOE	Apolipoprotein E	Protein Coding	61	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	13	4.39
ADSS	MAPK14	Mitogen-Activated Protein Kinase 14	Protein Coding	62	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	89	4.39
BTBD3	CUL1	Cullin 1	Protein Coding	55	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	143	1.47
BTBD3	SKP1	S-Phase Kinase Associated Protein 1	Protein Coding	52	Parkinson’s Disease, LRRK2, neurodegeneration	3	310	1.47
BTBD3	E2F1	E2F Transcription Factor 1	Protein Coding	53	Parkinson’s Disease, LRRK2, neurodegeneration	3	1777	1.47
BTBD3	DAPK1	Death Associated Protein Kinase 1	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	823	1.47
BTBD3	PLCB1	Phospholipase C Beta 1	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	1019	1.47
RTCA	LMNB1	Lamin B1	Protein Coding	57	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	228	1.23
RTCA	NOP56	NOP56 Ribonucleoprotein	Protein Coding	51	Parkinson’s Disease, late-onset, neurodegeneration	3	373	1.23
RTCA	IL6	Interleukin 6	Protein Coding	59	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	197	1.23
RTCA	HNRNPA1	Heterogeneous Nuclear Ribonucleoprotein A1	Protein Coding	56	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	538	1.23
RTCA	TNF	Tumor Necrosis Factor	Protein Coding	63	Parkinson’s Disease, LRRK2, late-onset, neurodegeneration	4	185	1.23

EnrichR Enrichment

KEGG

Wikipathways

Reactome

GO Cellular Component

GO Biological Process

GO Molecular Function

Final PD Report

Claire Green

12/06/2018

Data Sets